Advances in cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists / 药学实践杂志

Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.

Efectos cardiovasculares de los nuevos fármacos no insulínicos en diabetes / Cardiovascular effects of new non-insulinic anti-diabetes drugs]

La diabetes mellitus constituye actualmente un grave problema de salud pública a nivel mundial, que incrementa el riesgo de presentar complicaciones tanto microvasculares como macrovasculares. Aunque lograr los objetivos de glucemia recomendados reduce el riesgo de complicaciones microvasculares, el efecto de los fármacos para tratar la hiperglucemia sobre las complicaciones macrovasculares y la muerte cardiovascular es motivo de preocupación. En este contexto, las agencias regulatorias han modificado la normativa para la aprobación de nuevos fármacos en diabetes, de forma que establecen la necesidad de demostrar que son capaces de disminuir la glucemia junto con una evaluación sólida de la seguridad cardiovascular. El objetivo de este trabajo es revisar los efectos cardiovasculares de las nuevas familias de fármacos no insulínicos, en especial en su efecto sobre el riesgo de eventos cardiovasculares mayores. En los últimos años, finalmente, se ha confirmado que algunos fármacos para tratar la diabetes no solo son seguros desde el punto de vista cardiovascular, sino que incluso han mostrado capacidad para reducir el riesgo de enfermedad cardiovascular en la diabetes mellitus tipo 2. La evidencia obtenida ha determinado la actualización de algunas guías terapéuticas vigentes cuando el riesgo cardiovascular debería considerarse una variable fundamental al momento de la elección terapéutica en pacientes con diabetes.

Diabetes mellitus is currently a serious public health problem worldwide, that increases the risk of presenting microvascular and macrovascular complications. Although achieving the recommended blood glucose goals reduces the risk of microvascular complications, the effect of the drugs used to treat hyperglycemia on macrovascular complications and cardiovascular death is a cause for concern. In this context, the regulatory agencies have modified the regulations for the approval of new drugs in diabetes, by adding the need to demonstrate that they are capable of lowering blood glucose levels together with a solid assessment of cardiovascular safety. The objective of this study is to review the cardiovascular effects of the new families of non-insulin drugs, with special emphasis on their effect on the risk of major cardiovascular events. In recent years, it has finally been confirmed that some of the drugs used to treat diabetes are not only safe from a cardiovascular point of view, but have even shown capacity to reduce the risk of cardiovascular disease in type 2 diabetes mellitus. The evidence obtained determined the updating of some current therapeutic guidelines when cardiovascular risk should be considered a fundamental variable at the time of therapeutic choice in patients with diabetes.

Seguridad cardiovascular de los antiinflamatorios no esteroides / Cardiovascular safety of non-steroidal anti-inflammatory drugs

Resumen Los antiinflamatorios no esteroides son fármacos ampliamente prescritos en la práctica médica, mientras que los efectos secundarios más frecuentes son de índole gastrointestinal, en los últimos 10 años se ha cuestionado su seguridad cardiovascular. Los inhibidores de la ciclo-oxigenasa 2 (COX 2) fueron cuestionados en su seguridad cardiovascular debido a los resultados del estudio Vioxx Gastrointestinal Outcomes Research (VIGOR). En esta revisión se analizan los resultados del estudio Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION), y sus repercusiones en las indicaciones actuales de estos fármacos.

Abstract Non-steroidal anti-inflammatory drugs are broad use drugs in the medical practice, their main adverse effects are gastrointestinal complications; however, in the last 10 years their cardiovascular safety has been questioned. The results from the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial challenged the cardiovascular safety of Cyclooxygenase-2 (COX 2) inhibitors. In this review, the results of the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial are analysed, as well as their impact on the latest indications for this family of drugs.

Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies

ABSTRACT The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle-related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium.

The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) Trial and Its Clinical Impact on Patterns of Prescription for Anti-Diabetes Medication / 임상당뇨병

Since 2008, the Food and Drug Administration has required cardiovascular (CV) safety trials for all anti-diabetic medications available in the USA. Thus, new agents like dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists have been tested in CV safety trials. The results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) were released last year. Of the sodium-glucose cotransporter 2 (SGLT2) inhibitors tested, empagliflozin demonstrated a CV benefit in this trial. Another study of the renal protective effects of empagliflozin was released this year. The mechanisms supporting the cardio- and reno-protective effects of empagliflozin remain controversial. Hemodynamic changes related to SGLT2 inhibitors via natriuresis and osmotic diuresis are one potential mechanism. The Canadian Diabetes Association and European Society of Cardiology recently suggested SGLT2 inhibitors as an optimal anti-diabetic medication for patients with type 2 diabetes with overt CV disease. Further studies elucidating the potential mechanisms of cardio- and reno-protective effects of SGLT2 are needed.

Sodium-glucose co-transporter-2 inhibitors as anti-diabetic agents: a review.

The incidence and prevalence of Type 2 diabetes mellitus (T2DM) have been increasing worldwide. However, existing therapeutic classes of anti-diabetic drugs are not adequately effective in achieving and maintaining long-term glycemic control in the most patients. The majority of the drugs control blood sugar without addressing the basic pathology of insulin resistance and relative defi ciency. Moreover, side effects such as hypoglycemia and weight gain, of both new and established drugs need to be considered prior to treating a patient. An emerging anti-hyperglycemic intervention, the sodium glucose co-transporter 2 (SGLT2) inhibitor acts by a novel mechanism. Under physiological conditions, SGLT2 accounts for 90% of the glucose re-absorption in the kidney, while the SGLT2 inhibitors result in an increase in urinary excretion of glucose and lower plasma glucose levels. Here, the pros and cons of SGLT2 inhibitors are considered, while approaching a patient with T2DM. The basic biochemistry and physiology underlying the mechanisms of SGLT2 inhibitors are discussed alongside its clinical pharmacology, with a focus on metabolic changes associated with urinary glucose loss. Finally, a consideration of Food and Drug Administration safety concerns associated with acidosis due to SGLT2 inhibitor usage is presented, to allow a complete understanding of the utility of these molecules in the light of existing T2DM therapies.

CARDIOVASCULAR SAFETY OF EXERCISE IN THE ELDERLY / 体力科学

Although regular physical activity has many beneficial health-related effects for the elderly, inappropriate or excessive exercise has been known to exaggerate or be associated with risk of cardiovascular events. Therefore, appropriate initial health screening, including medical evaluation and risk stratification, is vital to ensure or increase exercise safety.<BR>In the elderly, medical evaluation needs to focus on identifying the coronary risk factors or signs suggestive of cardiovascular disease, since coronary artery disease has been demonstrated to be the most common cause responsible for cardiovascular events during physical activity in the elderly. It is noteworthy that variability of physical fitness is high in the elderly and cardiovascular risk during exercise is greater in subjects with lower physical fitness. In risk stratification, there-fore, pre-assessment of physical fitness in addition to routine medical evaluation is pivotal.<BR>Exercise prescription must be based on risk stratification and/or complicating cardiovascular disease severity. Low-level exercise, for example, 40% of VO<SUB>2</SUB>max is recommended for high-risk subjects such as those with two or more coronary risk factors, suggestive cardiovascular disease, lower physical fitness, or flail order adults. Since most subjects have reported at least one prodromal symptom within one week of sudden death, it is very important to check the physical condition before exercise on each day. Although various arrhythmias are likely to be responsible for cardiac events during exercise, their complete prediction is seldom possible. Therefore, monitoring EGG during exercise contributes greatly to exercise safety.<BR>Further investigation is required for improvement of exercise safety for the elderly.